Bioprosthetic heart valve with strain matched leaflets

ABSTRACT

Heart valve leaflet selection methods and apparatuses which subject individual leaflets to loads and measure the resulting deflection to more reliably group leaflets of similar physical characteristics for later assembly in prosthetic heart valves. The deflection testing may be accomplished using a variety of test set ups which are designed to impart a load on the leaflet which simulates the actual loading within a heart valve. The results from a number of deflection tests are used to categorize individual leaflets, which data can be combined with other data regarding the characteristics of the leaflet to better select leaflets for assembly into a multi-leaflet heart valve. In one embodiment, the deflection test is combined with an intrinsic load test, and leaflets having similar deflection and intrinsic load values used in the same heart valve. One apparatus for testing the leaflets includes a frame for securing the arcuate cusp of the leaflet while the straight coapting edge remains free, to simulate the actual leaflet mounting configuration within the heart valve prosthesis. The frame may include a lower portion having a recess for the leaflet and plurality of receptor holes around the peripheral edge of the recess, and an upper portion having a plurality of needles which extend downward through the leaflet and into the receptor holes and secure the edges of the leaflet.

RELATED APPLICATIONS

[0001] The present application is a continuation of co-pending Ser. No.09/710,409, filed Nov. 11, 2000, which is a divisional of Ser. No.09/207,783, filed Dec. 9, 1998, now U.S. Pat. No. 6,245,105, which is adivisional of Ser. No. 08/833,176, filed Apr. 3, 1997, now U.S. Pat. No.5,961,549.

FIELD OF THE INVENTION

[0002] The present invention relates to prosthetic heart valves, andmore particularly to prosthetic heart valves comprised of leaflets thathave been strain tested and sorted according to strain response.

BACKGROUND OF THE INVENTION

[0003] Prosthetic heart valves are used to replace damaged or diseasedheart valves. In vertebrate animals, the heart is a hollow muscularorgan having four pumping chambers: the left and right atria and theleft and right ventricles, each provided with its own one-way valve. Thenatural heart valves are identified as the aortic, mitral (or bicuspid),tricuspid, and pulmonary valves. Prosthetic heart valves can be used toreplace any of these natural valves. The two primary types of prostheticheart valves known in the art are mechanical valves and bio-prostheticvalves. Mechanical valves include rigid leaflets and a pivotingmechanism, and bio-prosthetic valves utilize flexible tissue leaflets,typically mounted to a manufactured support frame. The present inventionprovides methods for selecting leaflets in bio-prosthetic valves.

[0004] Bio-prosthetic valves may be formed from an intact, multi-leafletporcine (pig) heart valve, or by shaping a plurality of individualleaflets out of bovine pericardial tissue and combining the leaflets toform the valve. The pericardium is a sac around the heart of vertebrateanimals, and bovine (cow) pericardium is commonly used to makeindividual leaflets for prosthetic heart valves. The bovine pericardiumis first harvested from the animal and then chemically fixed tocrosslink collagen and elastin molecules in the tissue and increase thetissue durability, before being cut into leaflets. Various physicalcharacteristics of the tissue may be examined before or after fixation.

[0005] One drawback faced by a patient having an implantedbio-prosthetic heart valve is the potential for calcification of theleaflets if the valve remains in place for an extended period of time(more than ten years). Calcification tends to make the leaflets lessflexible. A significant amount of research has been accomplished inmitigating calcification of bovine pericardial leaflets to lengthen theuseable life of the heart valve. Calcification may reduce theperformance of the heart valve, and thus, the highest quality materialsand design in the heart valve is required to forestall a failure of thevalve from excessive calcium deposits.

[0006] Despite the drawbacks of artificial heart valve material, overtwenty years of clinical experience surrounding implanted artificialheart valves has produced a proven track record of success. Research inextending the useful life of the bio-prosthetic valves continues,however. One aspect of designing heart valves which is very important inimproving their performance is the selection of the pericardial tissueused in the leaflets. In all heart valves, the natural action of theflexible heart valve leaflets, which seal against each other, or co-apt,is desirable. The difficulty in simulating the leaflet movement of anactual heart valve (especially a mitral valve) in a prosthetic valve isthat the leaflets used are “inanimate.” There are no muscularattachments to the leaflets as in the natural valve, and the prostheticleaflets must co-apt to function properly solely in response to thefluid pressures within the heart chambers. Indeed, natural coaptation ofthe leaflets in bio-prosthetic valves comprising a plurality ofindividual leaflets sewn together is particularly difficult, even whencompared to inanimate but intact valves, such as harvested porcinevalves.

[0007] Much of this research involves the mechanical properties of freshor fixed bovine pericardium. A good discussion of the various physicalproperties of fixed bovine pericardium is given in Simonescu, et al,Mapping of Glutaraldehyde-Treated Bovine Pericardium and TissueSelection For Bio-prosthetic Heart Valves, Journal of Bio-MedicalMaterials Research, Vol. 27, 1993. Simionescu, et al, recognized thesometimes striking variations in physical properties of the pericardialtissue, even in the same pericardial sac. Their research mapped outareas in individual pericardial sacs and tested those areas for fiberorientation, suture holding power, and thickness. In another paper bySacks, Bi-axial Mechanical Behavior of Fixed Bovine Pericardium, FifthWorld Biomaterials Congress, May-June 1996, the collagen fiberarchitecture within bovine pericardial tissue was examined and variousspecimens were tested in a bi-axial tester. The results indicated thatby presorting for uniform collagen fiber architecture, more uniformbio-pericardial specimens could be obtained for better controlled use inbioprosthetic applications. Finally, in another study, Zioupos, et al,Anisotropic Elasticitv and Strength of Glutaraldehyde Fixed BovinePericardium For Use In Pericardial Bioprosthetic Valves, Journal ofBiomedical Materials Research, Vol. 28, 1994, various tests wereperformed on fixed bovine pericardial tissue to determine thestress/strain behavior along various axes. The results suggest thatleaflets can be made from fixed bovine pericardium possessing pronouncedanisotropy in strength and stiffness along two orthogonal directions. Inthe leaflets circumferential direction, which bears most of the stressduring function, the stiffer pericardium is desired, while in the radialdirection, more flexible tissue is desired. Leaflets are thus cut frombulk tissue whose properties have generally been examined, and theleaflets categorized accordingly.

[0008] Despite the extensive research into bulk tissue characteristicsthere remains a need for a more reliable method of selecting leaflets toinsure maximum functional compatibility with the other leaflets in thedynamic operating environment of a prosthetic heart valve.

SUMMARY OF THE INVENTION

[0009] The present invention provides methods and apparatuses forselecting leaflets for use in producing multi-leaflet prosthetic heartvalves. The selection of leaflets to be combined in a heart valve isbased on grouping a plurality of leaflets by strain response to anapplied load which is designed to simulate physiological pressureswithin the heart. A stress load sufficient to stress the leaflets withina high modulus region of their stress/strain characteristic is appliedto each leaflet, and leaflets within a predetermined observed deflectionrange of each other are grouped together. In an exemplary embodiment,glutaraldehyde-fixed leaflets are stressed within a generally linear,high modulus region of the bulk tissue stress/strain curve, and thedeflection measured for grouping the leaflets. In one embodiment, thestrain response is observed relative to a deflection of bovinepericardium leaflets resulting from applying a load thereto, and two orthree leaflets from a group of leaflets having deflections within 0.030inches of each other are combined to form a prosthetic heart valve

[0010] One aspect of the present invention is a method of selectingleaflets for an implantable heart valve, including providing acollection of similarly sized leaflets, applying a load to each leaflet,observing the resulting strain response, and sorting the leaflets basedon their respective strain responses. The collection may be naturaltissue leaflets which are chemically fixed prior to testing. The naturaltissue leaflets may be made of bovine pericardium. In one embodiment,the load applied is sufficient to create an average stress in at leastsome of the leaflets of between 300 and 600 kPa. The load is preferablyapplied for a predetermined number of times prior to observing thestrain response. Another aspect of the invention is a bioprostheticheart valve manufactured with leaflets selected by the aforementionedmethod, wherein the number of leaflets selected may be three.

[0011] The present invention also provides a method of testing a leafletfor use in an implantable heart valve, including mounting the leaflet ina frame so that portions which are to be sutured in the valve are heldstationary. A load is applied to the leaflet in a location adapted tosimulate a point at which an average load is applied in the valve, andthe resulting strain in the leaflet is sensed. The natural tissueleaflet typically defines a cusp and a coapting edge generally oppositethe cusp, and the step of mounting may comprise holding stationary atleast the cusp of the leaflet. The leaflet may be positioned in aframing assembly having a recess for receiving at least the edges of thecusps of the leaflet, and a cavity circumscribed by the recess.Moreover, the load may be applied by a mechanical deflector to an uppersurface of the leaflet over the cavity. Preferably, the framing assemblyincludes an upper member and a lower member, the lower member having therecess and the upper member shaped to mate over the recess. The methodfurther includes piercing the leaflet edges with needles extendingbetween and supported from movement by the upper and lower members.

[0012] The present invention provides an apparatus for testing heartvalve leaflets having a leaflet framing assembly including a holder witha recess for receiving a leaflet to be tested and a frame whichcooperates with the holder to hold stationary the cusps of the leaflet.The apparatus includes a base having indexing structure for locating theframing assembly thereon, and a deflection assembly indexed with respectto the base and having a deflector mounted for movement above theframing assembly to contact the leaflet. The recess may be cusp-shaped,and the holder includes a cavity substantially surrounded by the recessover which the leaflet is suspended. The apparatus may further includestructure adapted to hold stationary discrete points of the leafletaround the cavity. To secure discrete points of the leaflet around thecavity, the frame preferably includes a plurality of needles havingtheir pointed ends downward, and the recess includes receptor holes forthe needles, wherein the cusp of the leaflet is secured against movementat the discrete points defined by the needles.

BRIEF DESCRIPTION OF THE DRAWINGS

[0013]FIG. 1 is a front perspective view of an exemplary leaflet testerillustrating the principles of the present invention;

[0014]FIG. 2 is a rear perspective view of the leaflet tester of FIG. 1;

[0015]FIG. 3 is a perspective view of a leaflet mounting frame for usein the leaflet tester;

[0016]FIG. 4 is an exploded perspective view of the leaflet mountingframe and a needle calibration gauge for use therewith;

[0017]FIG. 5 is a perspective view of an exemplary leaflet holder foruse in the leaflet tester;

[0018]FIG. 6 is an exploded perspective view of the leaflet mountingframe over the leaflet holder, with a leaflet held therein;

[0019]FIG. 6a is a top elevational view of the leaflet holder, withleaflet therein, taken along line 6 a-6 a of FIG. 6;

[0020]FIG. 7 is an assembled perspective view of a leaflet framingassembly comprising the leaflet mounting frame, and leaflet holder;

[0021]FIG. 8a is an elevational view of a deflector in contact with aleaflet to be tested and mounted within the framing assembly prior to adeflection test;

[0022]FIG. 8b is a front elevational view of the framing assembly with aleaflet support removed and the deflector deflecting a leaflet;

[0023]FIG. 9 is a graph showing tissue deflection values for a pluralityof 29 mm CEP mitral valve leaflets;

[0024]FIG. 10a is a graph showing a distribution of deflection valuesfor a number of leaflets which have been previously grouped andcategorized by droop characteristic, Category A;

[0025]FIG. 10b is a graph showing a distribution of deflection valuesfor a number of leaflets which have been previously grouped andcategorized by droop characteristic, Category B;

[0026]FIG. 10c is a graph showing a distribution of deflection valuesfor a number of leaflets which have been previously grouped andcategorized by droop characteristic, Category C.; and

[0027]FIG. 11 is a graph illustrating a typical stress-strain curve forpericardial tissue.

DESCRIPTION OF THE EXEMPLARY EMBODIMENTS

[0028] The present invention involves testing individual leaflets foruse in producing heart valves which, in its broadest sense, providesmethods and apparatuses for obtaining and grouping the deflectionresponse of individual leaflets in order to better sort or group themfor later selection and combining with other leaflets to form a valve.Unlike prior art bulk tissue testing, the present inventioncharacterizes individual leaflet response under loads similar to thosethe leaflets are subjected to under normal physiological conditionswithin the heart. Not only are the loads higher than previously used intissue testing, but the leaflets are subjected to repeated loadings,which conditions the leaflet tissue, prior to observing a deflection.Although the bulk mechanical properties of tissue in general have beenstudied, prior art non-destructive tests of individual tissues alreadycut to leaflet shape have not been developed or utilized to group tissueleaflets for assembly into prosthetic valves.

[0029] An exemplary deflection testing apparatus, disclosed within theteachings of the present invention, closely simulates dynamic pressureon the individual leaflets with a mechanical deflector having a smooth,generally spherical tip on the end for repeatedly contacting a framedand supported leaflet at a pre-determined contact location. The leafletis framed and secured around its periphery at a number of discretepoints designed to simulate the lines of suturing that would retain theleaflet within an actual prosthetic heart valve. The invention shouldnot be limited to the specific apparatus shown, however, and is intendedto cover any equivalent apparatuses or methods which take individualleaflets and subject them to loading while measuring their deflectionresponse. For example, an alternative apparatus contemplated as beingwithin the scope of the present invention may apply a pressure to theleaflet, as opposed to a discrete or diffuse mechanical load.

[0030] Exemplar Deflection Tester Apparatus

[0031] One particular embodiment of a leaflet deflection tester 20 forloading individual leaflets is shown in FIGS. 1 and 2. Referring to FIG.1, the leaflet deflection tester 20 comprises a flat base 22 supportinga leaflet framing assembly 24 and a deflector assembly 26 thereabove. Aleaflet 28 is shown mounted within the framing assembly 24 and adeflector 30 is positioned to apply a load to the leaflet to result in adeflection which can be read from display 32. For purposes ofdiscussion, the display 2 faces in a forward longitudinal direction, andlateral left and right directions are defined from the perspective oflooking at the display.

[0032] The deflector assembly 26 comprises a support post 34 verticallyoriented with respect to the base 22 and attached thereto with a postholder 36. Referring to FIG. 2, at the top of the post 34, a cap 38 isvertically adjustable via a set screw 40 engaging a vertical groove 42in one side of the post. An indicator carriage 44 is also verticallyadjustable along the post and may be secured at various locations usinga pair of carriage locking screws 46 which also engage the groove 42. Acarriage arm 48 extends longitudinally forward from the post 34 andterminates in a position indicator 50 mounted thereto. Referring to FIG.1, the position indicator preferably includes electronic circuitry and adigital readout 32, but may be of a variety of configurations, and theparticular embodiment illustrated herein should not be construed aslimiting. Control buttons 51 including a zero reset function areprovided on the face of the indicator 50.

[0033] The position indicator 50 is generally centrally located abovethe leaflet framing assembly 24 and includes an indicator shaft 52,vertically passing therethrough and engaging position-sensing equipmentwithin the indicator. That is, various known mechanical orelectromechanical devices for sensing the displacement of a shaft withina housing are contemplated for this purpose and will not be describedfurther herein. A mass 54 attaches to an upper end of the indicator 52above the position indicator 50. At the lower end of the shaft 52, acollar 56 is fastened thereon via a locking screw 58. The collarcontinues downward and terminates in the aforementioned deflector 30.

[0034] The deflector assembly 26 further includes a means for verticallyadjusting the position between the post cap 38 and the indicatorcarriage 44. A vertical adjustment knob 60 is mounted for rotation abovea vertical axis through the post cap 38. The adjustment knob 60 engagesa connecting rod 62 which extends between the post cap 38 and theindicator carriage 44. In one embodiment, the vertical adjustment knob60 rotates a threaded nut within the post cap 38 which engages malethreads on an upper end of the connecting rod 60 to cause its verticaldisplacement. The connecting rod 62 is preferably firmly connected tothe indicator carriage 44 and thus turning the vertical knob 60vertically displaces the indicator carriage 44. The use of the verticaladjustment knob 60 in calibrating and operating the tester 20 will bedescribed below.

[0035] With reference still to FIG. 1, and, more particularly, to therear perspective view in FIG. 2, the post holder 36 is formed as amonolithic T-shaped block, having a pair of overhanging edges throughwhich longitudinally oriented adjustment slots 68 are provided. Theslots 68 are provided on either lateral side of the support post 34 andreceive locking bolts 70 which extend downward into engagement with astep 72 formed in a longitudinal adjustment bracket 74. The longitudinaladjustment bracket 74 can thus be adjusted longitudinally with respectto the post holder 36 and secured with the bolt 70.

[0036] On a front end of the longitudinal adjustment bracket 74, anoverhanging portion includes a lateral adjustment slot 76 receiving alocking screw 78. Referring to FIG. 1, the locking screw 78 continuesthrough the overhanging portion of the adjustment bracket 74 intocontact with a step 80 formed in a lateral adjustment bracket 82 whichis generally L-shaped, having a forwardly extending arm portion 84. AnL-shaped clamp 86 is adjustable longitudinally with respect to the armportion 84 and is fastened thereto with a pair of clamping screws 88.The combination of the adjustment brackets 74 and 82, and L-shaped clamp86, index and secure the leaflet framing assembly 24 with respect to thesupport post 34 and, in turn, the position indicator 50.

[0037] An upper framing assembly member or leaflet mounting frame 94,illustrated in FIGS. 3 and 4, comprises a generally rectangular shapedbase 96, having an upper stepped recess 98 open to a front side of therectangle. An undercut 100 is formed in the recess 98 to receive aplate-shaped needle clamp 102 therein. The needle clamp 102 includes asemicircular cutout 104 in an edge facing toward the open edge of therecess 98. The cutout 104 conforms to a semicircular cutout 106 formedin the base 96. It should be noted that although the cutouts 104, 106are described as generally semicircular, the particular shape of theleaflet 28 may be somewhat oval in shape, which may correspondinglyalter the shape of the cutouts.

[0038] Both the base 96 and the needle clamp 102 include a plurality ofregistered, vertical through holes 108, arranged equidistantly aroundthe semicircular cutouts 104 and 106. In a preferred embodiment, thereare seven such through holes 108, arrayed at specific circumferentialangles around the cutouts 104 and 106. The through holes 108 receiveleaflet framing needles 110 which are vertically retained thereinthrough the use of a needle clamp screw 112 threaded through a rear wallof the frame body 96 and into contact with the needle clamp 102.

[0039] The frame base 96 further includes a plurality of positioningtabs 114 depending downward therefrom. In the illustrated embodiment,there are three such tabs 114, two on left and right sides,respectively, of the frame base 96 and one on the rear side. Withreference to FIG. 4, the tabs are utilized to orient a needle gauge orcalibration member 116 under the cutouts 104 and 106. More particularly,the needle gauge 116 comprises a generally rectangular base 118 and arecessed pocket 120. The base 118 is guided between the two side tabs114 and abuts against the rear tab of the mounting frame 94. In thisorientation, the pocket 120 is positioned directly below all of thethrough holes 108 so that the needles 110 depend downward below thelower surface of the frame base 96, as seen at 122, only as far as thepocket. The needles 110 are inserted through the holes 108 into contactwith the pocket 120, and then the needle clamp screw 112 is tightened topush the needle clamp 102 in a direction out of the recess 98 and createa compression against the needles 110. That is, the shear force exertedon the needles 110 by the through holes 108 in the frame base 96 andneedle clamp 102 maintains the needles in the vertical position ascalibrated by the needle gauge 116. Once the needles are calibrated todepend downward the same distance, the frame 94 is ready for use in theframing assembly 24.

[0040]FIG. 5 illustrates a lower framing assembly member or leafletholder 126 comprising a block-shaped body 128 having a flat lowersurface adapted to rest on the base 22 (FIG. 1) and a flat upperplatform 130. The body 128 is generally rectangular in shape andincludes a rectangular base locator 132 projecting from a front side andshorter in height than the body 128. The outer edges of the body 128,other than the edge from which the base locator 132 extends, includepositioning channels 134 opening to the platform 130. The positioningchannels 134 receive the positioning tabs 114, previously described forthe leaflet mounting frame 94, as best seen in FIG. 6, to locate themounting frame with respect to the leaflet holder 126. The lower surfaceof the leaflet mounting frame base 96 is flat and is juxtaposed with theflat platform 130. In the center of the body 128, and opening toward thebase locator 132, a cavity 136 is formed having a generallysemicylindrical shape. A stepped leaflet edge recess 138 is formed inthe platform 130 surrounding the cavity 136 and is sized and shaped toreceive a leaflet, such as the leaflet 28 as shown in FIGS. 1 and 2.

[0041] Referring to FIG. 5, a paddle-shaped leaflet support 140 has agenerally semicircular end which fits closely within the cavity 136,with a handle 142 extending outward from the cavity 136 and resting on atop surface of the base locator 132. The leaflet support 140 has aheight which is identical to the height from the top surface of the baselocator 132 to the elevation of the leaflet edge recess 138 so that theupper surface of the leaflet support 140 is in the same plane as theedge recess 138. The edge recess 138 further includes a plurality ofneedle receptor holes 144 sized and positioned in an array identical tothe array in which the through holes 108 and associated needles 110 arepositioned around the leaflet mounting frame 94. This arrangement allowsthe needles 110 to extend through the peripheral edge of the leaflet 28into the receptor holes 144, thus holding stationary portions of theleaflet at the edge recess 138.

[0042] With reference to FIG. 6a, the leaflet typically includes astraight coapting edge 148 having opposed tab ends 150, and a generallysemicircular cusp 152 therebetween and opposite the coapting edge. Thetab ends 150 include angled sides 153 transitioning to the coapting edge148. The edge recess 138 is sized and shaped to receive the cusp 152 andtabs 150 with the coapting edge 148 oriented parallel with but spacedfrom a front edge of the holder 126.

[0043]FIG. 6a also illustrates a point 154 at which an axis through thecenter of the deflector 30 intersects the leaflet 28. This point 154will be referred to herein as the point of contact between the deflector30 (FIG. 1) and leaflet 28, but in the exemplary embodiment thedeflector is a relatively large diameter smooth hemisphere, and contactsthe leaflet over a circular area to better simulate a distributed loadand to help avoid stress risers. The point 154 is determined from amodel of the stress distribution in the leaflet based on assumed forcesapplied to the leaflet in a human heart valve. The forces applied to theleaflet in a human heart valve originate from fluid pressures upstreamand downstream of the valve, and the stress distribution is found fromthe leaflets' shape and boundary conditions (i.e., geometry of the linesof sutures attaching the leaflets in the valve). The point 154 is thusan idealized concentrated load point (or concentrated area) equivalentto the actual distributed pressure load.

[0044] The leaflet is symmetrical about an axis perpendicular to andbisecting the coapting edge 148, and is typically continuously suturedin an actual valve along the cusp 152, and thus the point 154 isdesirably on that axis. The dimension “A” is the distance from the point154 to the coapting edge 148 determined from the aforementioned stressdistribution model. The dimension “A” will vary depending on the sizeand geometry of the leaflet, its thickness and bulk material properties,and the assumed stress distribution. It will be noted, however, that thepoint 154 is spaced from the coapting edge 148, which prevents unduetensile stresses between the deflector 30 and the points closest to thecoapting edge at which the leaflet is held stationary in the framingassembly 24 (i.e., needles 110, as will be described below). Theparticular apparatus and methods disclosed, and the concentratedloading, requires that the point 154 be spaced from the coapting edge148 to best distribute the tensile stresses between the deflector 30 andthe stationary points at the leaflet periphery. Of course, those ofskill in the art will recognize that a more accurate test setup withactual suturing around the cusp 152 and a pressure loading over thesurface of the leaflet could be substituted within the scope andteaching of the present invention, and the presently illustrated testsetup is an approximation driven by practical manufacturingconsiderations.

[0045] The interaction of the leaflet mounting frame 94 with the leafletholder 126 will be explained with reference to FIGS. 6 and 7. Asmentioned, the positioning tabs 114 fit within the positioning channels134 to orient the mounting frame 94 with respect to the leaflet holder126. The registration between the tabs 114 and channels 134 insures thatthe needles 110 in the through holes 108 in both the base 96 and needleclamp 102 of the mounting frame 94 align with the needle receptor holes144 in the leaflet holder 126. The assembly arrow 146 illustrates themovement of the mounting frame 94 when coupling to the leaflet holder126. In an anticipated alternative embodiment, the mounting frame 94will be hingedly or otherwise pivotally coupled to the holder 126, withthe final relative movement being vertical to avoid skewing the needleswithin the receptor holes 144.

[0046] The leaflet 28 is pre-positioned so that its outer edges conformto the shape of the leaflet edge recess 138, and the middle portion issupported by the leaflet support 140. The needles 110 extending downbelow the leaflet mounting frame 94 thus pierce and pass through thetissue of the leaflet 28 and extend into the receptor holes 144. In aheart valve, the cusps 152 of each leaflet are supported by a wireform,and the coapting edges 148 remain free to cooperate with the coaptingedges of the other leaflets. The framing assembly 24 thus closelysimulates the static points of attachment so that the stressdistribution, and accompanying deflection response, in the leaflet 28 isas near to the actual distribution as possible. The needles 110 holdstationary peripheral portions of the leaflet 28 to approximate anactual line of sutures peripherally securing the leaflet within a heartvalve. Furthermore, the lower surface of the mounting frame base 96rests on the upper surface of the platform 130. In this regard, it isimportant to note that the leaflet 28 is preferably not compressed, oronly lightly compressed, by the weight of the mounting frame 94 becauseit is positioned within the recess 138. The final assembled leafletframing assembly 24 is illustrated in FIG. 7.

[0047]FIGS. 8a and 8 b illustrate two positions of the deflector 30during a leaflet deflection test. The leaflet 28 is mounted in theframing assembly 24 with the leaflet support 140 supporting the leaflet28 from underneath in a plane at the same elevation of the leaflet edgerecess 138, and thus the leaflet 28 does not bend or sag in itsmid-portion. The deflector 30 is lowered into a position just contactingthe top of the leaflet 28, as shown in FIG. 8a, prior to a deflectiontest. Subsequently, the leaflet support 140 is removed from underneaththe leaflet 28, and the indicator shaft 52 is allowed to drop as in FIG.8b, thus causing the deflector 30 to displace the leaflet 28 until anequilibrium is reached. The equilibrium depends on the framing geometry,the size of the mass 54 (FIG. 1), and the stress/strain characteristicsof the leaflet 28. The total deflection of the leaflet at the point ofcontact with the deflector 30 is illustrated in FIG. 8b by the dimension“d”. As described below in the Exemplary Test Assembly section, anapproximate measurement of the true deflection “d” is made bydisregarding the relaxed thickness of the leaflet being tested forsimplicity of calibration of the apparatus and method.

[0048] Preferably, the deflector 30 is a relatively large diametersmooth hemisphere so that the load imposed on the upper surface ofleaflet 28 is somewhat distributed. The deflector 30 is made of abiocompatible material, such as a plastic, and preferably athermoplastic. Other variations of deflector 30 are envisioned and thepresent invention should not be construed to be limited to theillustrated embodiment. For example, a more uniformly distributed loadsuch as a pressure load may be imposed upon the leaflet 28 and thesubsequent deflection measured. In all cases, the aim is to closelysimulate the conditions experienced by the leaflet 28 in an actual heartvalve. Indeed, it would be desirable to load test leaflets after beinginstalled on a heart valve wireform and support ring. However, even ifsuch a test could be accurately configured, it would be difficult totest individual leaflets within a three leaflet prosthetic valve, forexample. Furthermore, once the valve has been constructed, many of thebenefits of the leaflet selection process are rendered moot. That is,the primary consideration is finding similar leaflets to combine withina single heart valve. A secondary consideration, which is notinsignificant, is being able to select a leaflet prior to constructionof the valve to reduce manufacturing time and expense. Construction of aheart valve involves many intricate steps of sewing leaflets togetherand to the wireform and surrounding fabric covering. The work must bedone by highly skilled technicians and thus testing of individualleaflets within fully constructed valves is prohibitively expensive,although not outside of the scope of the present invention.

[0049] The present invention thus seeks to provide a selection methodfor individual leaflets prior to construction of a heart valve whichmost accurately predicts the ultimate mechanical response of eachleaflet within the constructed valve and ensures optimum performance incoaptation with the other leaflets. To that end, the presentlyillustrated test apparatus 20 is believed to closely simulate the forcesand stresses imposed on the leaflet during use, in a relatively easy toset up and operate environment. Because of the modular nature of thetest apparatus 20, repeatability of tests for various sizes of leafletsis enhanced. That is, the leaflet holder 126 is sized for a particulardiameter of leaflet, and a number of leaflet holders having differentleaflet edge recesses 138 may be provided for different sized leaflets.The external dimensions of the leaflet holder 126 remain the same sothat it may be indexed within the aforementioned brackets on theplatform 22 (FIG. 1) and the same deflection assembly 26 is utilized.Concurrently, the leaflet mounting frame 94 may be provided in a varietyof sizes to cooperate with different sized holders. An additionaladvantage is the relatively small size and portable nature of the tester20. The platform 22 may be set up on assembly lines, laboratory tables,and even desktops.

[0050] Exemplary Test Assembly

[0051] The steps in preparing the exemplary tester apparatus 20 for usewill now be described with respect to the drawings. First of all, theequipment is cleaned to remove any particulate matter and dirt adheredthereto. The test equipment is then sterilized through a processincluding a bio-burden reduction process (BREP) well known in the art.

[0052] With reference to FIGS. 1 and 2, the post cap 38 is first securedon the post 34 by tightening the set screw 40. The locking screws 46 areloosened to allow the carriage 44 to freely move vertically on the post34. Additionally, the locking bolts 70, locking screws 78, and clampingscrews 88 are loosened. Prior to installing the leaflet framing assembly24, the framing assembly 24 must be indexed under the deflector assembly26. To accomplish this, an indexing tip (which is not shown) is fastenedto the lower end of the indicator shaft 52 in place of the collar 56 anddeflector 30. The indexing tip on the lower end of the indicator shaft52 fits through an indexing hole (not shown here) within the cavity 136formed in the leaflet holder 126. The indexing hole allows the indexingtip to contact the platform base 22. Once the indexing tip has contactedthe base 22, the carriage locking screws 46 are tightened to locate thecarriage 44. As the indexing hole is sized just large enough to receivethe indexing tip, the leaflet holder 126 is located in its properposition with respect to the position indicator 50. That is, thevertical axis of the indicator shaft 52 is positioned at the preciselocation with respect to the leaflet holder 126 so that the deflector30, when eventually installed, will contact the leaflet 28 in the properposition.

[0053] The longitudinal adjustment bracket 74 and lateral adjustmentbracket 82 are then manipulated to contact the framing assembly 24 underthe deflector assembly 26. The longitudinal adjustment bracket 74 andlateral extending portion of the lateral adjustment bracket 82 aredisplaced to contact the associated sides of the leaflet holder 126, andthe arm portion 84 contacts the end of the base locator 132. The lockingbolts and locking screw 78 are tightened. The carriage locking screws 46are then loosened and the vertical adjustment knob 60 manipulated toraise the carriage 44 upward. The indexing tip is removed.

[0054] The correct size deflector 30 is chosen depending on the size ofthe leaflet 28 to be tested. The collar 56 of the deflector 30 isattached to the lower end of the indicator shaft 52 via the lockingscrew 58. Next, the proper size mass 54 is selected for the leaflet 28to be tested. In this regard, a single mass for a particular size ofleaflet 28 is preferred, although different masses may be used on thesame leaflet for a variety of deflection results. The mass 54 must beselected so as not to over stress the leaflet 28 being tested. Thus, forexample, stress loading for a glutaraldehyde-fixed pericardial tissueleaflet within a mitral valve is up to 1,000 kPa For this application,therefore, the mass 54 should be chosen so that the stress imparted tothe leaflet 28 is no greater than 1,000 kPa.

[0055] At this point, the position indicator 50 is calibrated. With theleaflet support 140 in position, the position indicator 50 is reset sothat the display 32 reads zero, using one of the control buttons 51. Thecarriage locking screws 46 are then loosened and the entire positionindicator 50 is lowered using the vertical adjustment knob 60 on the topof the post cap 38. The carriage 44, along with the position indicator50, is lowered until the deflector 30 contacts the upper surface of theleaflet support 140. The vertical adjustment knob 60 is further turnedto lower the position indicator 50 while the indicator shaft 52 remainsstationary until the display 32 reads a deflection of betweenapproximately 0.390″ and 0.410″. Then the carriage locking screws 46 aretightened to lock the position indicator 50 in place.

[0056] The display 32 is then again set to a zero reading, using one ofthe control buttons 51. This sequence ensures that the deflector 30 candrop a sufficient distance below the level of the leaflet support 140 toensure the leaflet under test is properly stressed (i.e., notunderstressed). That is, a proper deflection reading is desirablyobtained within a nearly linear, high modulus region of the particularleaflet stress/strain curve, prior to reaching the yield stress, asdescribed below with reference to FIG. 11. In general, the optimumstress level is first approximated, and the mass and total allowabledeflection selected accordingly from that approximation to result instress in a linear region of the tissue stress/strain curve.

[0057] It should be noted that the leaflet deflection is measured from azero datum of the top of the leaflet support 140, and the thickness ofthe particular leaflet is disregarded. The leaflet thickness isrelatively small in comparison to the deflection, and the ultimate testresults are used to compare leaflets, so the slight inaccuracy from nottaking the leaflet thickness into account applies to all of theleaflets, and is thus rendered even less important. Thus, the dimension“d” indicated in FIG. 8b is the true deflection, while the deflectionactually measured is off by the relaxed thickness of the leaflet beingtested, and is a close approximation of the true deflection.

[0058] The next step in the test preparation process is to secure theleaflet 28 within the framing assembly 24. First, the leaflet mountingframe 94 is assembled by inserting the needle clamp 102 in the base 96.As mentioned previously, the appropriately sized base 96 and needleclamp 102 are chosen for the particular leaflet 28 being tested. Theneedles 110 are inserted into the through holes 108, until their tipsjust extend beyond the lower surface of the base 96 as seen in FIG. 4.Of course, throughout this operation, the needle clamp screw 112 isloose to remove any shear force between the needle clamp 102 and thebase 96.

[0059] As shown in FIG. 4, the leaflet mounting frame 94 is thenpositioned over the needle gauge 116 on a flat surface and the needles110 allowed to drop until their lower tips contact the upper surface ofthe pocket 20. At this stage, the needle clamp screw 112 is tightened toapply a shear between the needle clamp 102 and the base 96, which holdsthe needles 110 in their calibrated elevation. The needles 110 areindividually pulled to insure that they are tightly held in the properposition and if any of the needles move, the needle clamp screw 112 isrecalibrated and tightened further. Before placement of the leaflet 28within the leaflet holder 126, the leaflet mounting frame 94 is firstpositioned over and mated with the leaflet holder to insure that theneedles 110 register with and extend freely into the receptor holes 144.The mounting frame 94 is then removed from the leaflet holder 126.

[0060] The leaflet support 140 is then installed in the cavity 136 ofthe leaflet holder 126, and the leaflet 28 to be tested positioned onthe leaflet support so that its peripheral edges conform to theappropriately sized leaflet edge recess 138. The mounting frame 94 isthen brought vertically over the leaflet holder 126 and displaceddownward so that the needles 110 pass through the tissue of the leaflet28 and into the receptor holes 144. In its assembled state, as shown inFIG. 7, the lower surface of the base 96 rests on the upper surface ofthe platform 130, with the positioning tabs 114 oriented in thepositioning channels 134. In this arrangement, therefore, the peripheraledges of the leaflet are not pinched or otherwise compressed between theframing assembly halves. This helps reduce damage to the leaflet whichmay be assembled in a prosthetic valve and implanted for use in apatient.

[0061] The leaflet framing assembly 24 with leaflet 28 mounted thereinis then placed back into its previously indexed position under thedeflector assembly 26. The L-shaped clamp 86 is brought into contactwith the side of the base locator 132, and the clamping screws 88tightened to secure the framing assembly 24 on the base 22.

[0062] At this point, the deflector 30 is elevated manually with theposition indicator 50 remaining stationary. The deflector 30 is thenplaced gently on the top of the leaflet 28 by manually lowering theshaft 52. The leaflet support 140 is then removed carefully fromunderneath the leaflet 28 which is allowed to deflect under the weightof the mass 54. The deflector 30 is elevated away from contact with theleaflet 28, and the test is repeated several times to insure correctreadout. Preferably the leaflet 28 is deflected five times, and thereadouts of the fourth and fifth deflections are then recorded.

[0063] Upon removal of the leaflet mounting frame 94, the leaflet 28should stay with the frame by virtue of the needles 110 piercing theleaflet tissue. If all seven of the needle tips are visible through theleaflet tissue, then the leaflet 28 is removed from the mounting frame94 by loosening the needle clamp screw 112 and pulling the needles 110out from above. The leaflet 28, if useable, is then placed in itsparticular deflection grouping and stored for later combination withsimilar leaflets to produce a heart valve.

[0064] If any of the needles 110 are not visible through the tissue,then the mounting frame 94 is reinstalled onto the leaflet holder 126.After removing the mounting frame 94 once again, the needle tips shouldbe visible through the leaflet 28. When all the needle tips are visiblethrough the leaflet 28, the mounting frame 94 is replaced on the leafletholder 126 and one or more deflection tests are repeated. The data fromthe second set of deflection tests are then used to select and classifythe leaflet for later grouping with other leaflets. After this secondtest, the leaflet 28 is removed from the mounting frame 94 and placed inits particular deflection grouping.

[0065] Exemplary Tissue Selection Methodology

[0066] Studies in the prior art have demonstrated there can be asignificant variation in the stress/strain curves from specimen tospecimen of pericardial tissue. Tests have also demonstrated thattypical stress loading of glutaraldehyde-fixed pericardial tissueresults in varying strains for different tissue samples, even from thesame pericardium sac. Moreover, leaflets may experience localizedstresses within a mitral valve of up to 1,000 kPa, with a typical highaverage range of between 500 and 600 kPa. Previous studies have shownthat the average stress/strain curve of leaflet tissue materialnon-linearly increases until a particular stress is reached after whichthe curve is approximately linear (the tissue stretches significantlymore at low loads). In general, tissue is significantly stiffer in thehigh stress region, and is more flexible at low stresses.

[0067]FIG. 11 illustrates a typical stress-strain curve for pericardialtissue. It will be understood that the curve is exemplary for aparticular tissue fixed in a particular way. Other tissues may responddifferently, but the trends shown are generally seen in fixed bovinepericardium tissue. The curve shows a low elastic modulus of the tissueat low stresses under about 300 kPa, and an increasing modulus at higherstresses. The curve is generally linear above about 300 to 600 kPa. Forpurposes of discussion, a high modulus region (HMR) of the curve isshown in FIG. 11 within which the stress/strain curve is generallylinear. The HMR is an approximation of an average high stress rangewithin a particular fixed bovine pericardium leaflet in an implantedheart valve. This approximate information can be combined with knowledgeof the operating conditions and valve size to design an appropriatedeflection test method. That is, the bulk tissue stress/strain curvealong with the valve size and assumed loading and boundary conditionscan be combined to predict a stress distribution in the leaflet. Thesize of the mass 54 in the illustrated exemplary test apparatus 20 (FIG.1), for example, is then selected to stress the leaflet into the HMR ofthe tissue. Understressing the leaflet during the test may not obtainoptimum results, and over-stressing the leaflet may damage it. Thus, forexample, a preferred stress level applied to glutaraldehyde-fixedpericardial tissue leaflets for a 29 mm CEP valve in the testerapparatus 20 has been found to be in the HMR of between 300 and 600 kPa.

[0068] The present tissue deflection test addresses the observedvariation in resulting strain in tissue leaflets when the applied loadis similar to pressure loading under physiological conditions. Asmentioned previously, localized stresses on a leaflet in use may reach1,000 kPa. Testing of leaflets within the tester 20 is preferablyaccomplished using a significantly lower stress level, while stillsufficiently deflecting the leaflet in the linear stress/strain regionfor useful results. Empirical testing or finite element stress analysison specific leaflet material is desirably used to predict the -probablestress-strain relationship of individual leaflets. This preliminarytesting or analysis is then used to design the proper deflection testmethod, as described herein.

[0069] The particular testing stress level, however, is also affected bythe type of test configuration. The needles 110 secure the edges of theleaflet 28 in a uniform circumferential array which simulates thesutures which attach the leaflet cusp within a heart valve prosthesis.In particular, the cusp 152 of the leaflet 28 is held stationary atdiscrete points defined by the needles 110, while the coapting edge 148remains free. The number of needles 110 should be sufficient to simulatethis edge connection of the leaflet in use, but not be too numerous asthe needles pierce through the tissue of the leaflet. Therefore, betweenat least five and nine, and preferably at least seven needles 110 asshown are adequate for a uniform framing configuration of the leafletwithout creating an inordinate number of holes therein. As the load isapplied by the deflector 30 the stress distribution within the leaflet28 will not be completely uniform because the leaflet is only held atdiscrete locations. Therefore the load applied must be carefully gauged,so as not to create undue levels of stress concentration in and aroundthe points at which the needles pierce through the leaflet tissue. Thestated range of between 300 and 600 kPa for glutaraldehyde-fixedpericardial tissue leaflets has been determined to be suitable whenusing seven needles as shown. Of course, other arrangements for framingthe leaflet are possible, such as using more than seven needles, and thestress range may be appropriately modified. Further, the stress range isnot determined solely with reference to the leaflet holding arrangement.Those of skill in the art will recognize the exemplary test apparatus isan attempt to simulate true stresses imposed on the leaflet, withcertain tradeoffs, including simplifying the test apparatus andminimizing the number of needles used.

[0070] The mass 54 for a 29 mm CEP leaflet is chosen to be approximately100 g to set up stress 10 levels of between 300 and 600 kPa in theleaflet. The mass 54 for other size valve leaflets are scaled from the100 gram load used for the 29 mm valve leaflet, as seen in Table I.TABLE I Valve Leaflet Size Deflection Load (g) 25 mm 74 27 mm 87 29 mm100 31 mm 112

[0071] Additional testing may be performed to insure that theappropriate mass 54 selected for various valve size leaflets imparts astress in a generally linear region of the tissue stress/strain curve.One example of such testing is to use an Instron tensile test tester inplace of the position indicator 50. The Instron Tensile tester can beused to vary the load on the leaflet 28 and a series of stress/straincurves can be generated for each leaflet size. Based on these testresults, the minimum load on the tissue leaflets for all sizes to ensurethat the stress/strain response is in the linear regime is approximately60 grams.

[0072] Other means of categorizing leaflets may be used in conjunctionwith the presently described deflection test. For example, selection ofindividual leaflets to be grouped with other leaflets in a heart valvehas been accomplished by the assignee of the present invention using aso-called “droop” test of the leaflets. That is, the leaflets arecantilevered over the end of a rod, or other structure, and the droop ofthe leaflet for different lengths of extension is observed. The drooptest can thus be generally termed an intrinsic loading test, whereinthere is no applied load and the leaflet deflects solely under its ownweight. The droop test is used to categorize leaflets, so that leafletswith similar droop characteristics can be put together for assembly intoa heart valve in an attempt to improve leaflet cooperation andcoaptation. The droop test in combination with the presently describeddeflection test is particularly useful in grouping individual leafletswith similar characteristics for assembly into a multi-leaflet valve.

[0073] Results for loading of leaflets for use in various size valves isgiven in FIG. 9. After the leaflets were deflected five times insuccession to account for conditioning or change in the Young's modulus,a final deflection comprising the last observed deflection or an averageof the last two observed deflections were recorded. FIG. 9 shows thedistribution of deflection values from the tissue deflection test. Thedeflection values for the leaflets measured ranged from 0.19 to 0.36with the majority grouped between 0.23 and 0.30.

[0074] To illustrate the effectiveness of the methods and apparatuses ofthe present invention relative to conventional tissue categorizingtechniques, the droop test and tissue deflection test of the presentinvention were applied to 169 leaflets. The leaflets tested fordeflection response in FIG. 9 were then categorized by droop value.FIGS. 10a, 10 b, and 10 c show the population of leaflets categorized byletters A, B and C based on droop characteristic. In general, theleaflets from Group A had the lowest deflection values with Group Bsomewhere between Group A and Group C. There is significant overlap ofdeflection values between categories A, B, and C.

[0075] In an exemplary embodiment, the deflection test described hereinis first used to categorize a number of similarly shaped leaflets intosubgroups, such as is shown in FIG. 9. Subsequently, a droop test isperformed on a subgroup of leaflets within a predetermined deflectionrange, and only leaflets within an acceptable droop range from thatsubgroup are combined into a prosthetic heart valve. Alternatively, thedroop test may be performed first to obtain a number of subgroups, oneor more of which is then deflection tested to arrive at a selected groupof leaflets suitable for combining together in a prosthetic heart valve.

[0076] In an exemplary embodiment, the individual leaflets 28 aredeflection tested and leaflets are selected which produced a totaldeflection of between 0.170 and 0.340″ for valve sizes of 25 to 31 mm.Furthermore, for reliability, it is preferred that only leaflets be usedfor which the fourth and fifth readouts differ within a predeterminedrange, for example between plus or minus 0.003 inches.

[0077] To evaluate the effect of selecting and combining tissue leafletsin 29 mm CEP valves, four valves were manufactured and tested. Twoleaflets were selected to have similar deflection values. The thirdleaflet deflection value was varied from approximately 0.010″ to 0.040″compared to the as shown in Table II. TABLE II Deflection DeflectionValve Number of Leaflets 1 & 2 of Leaflet 3 Δ Deflection 13559 0.2980.310 0.012 13560 0.254 0.277 0.023 13561 0.238 0.269 0.031 13562 0.2770.317 0.040

[0078] The valves listed in Table II were placed into a pulsatile flowsimulator, and testing performed per conventional protocol. Thedifferential pressure for the testing was 200 mm Hg per Food and DrugAdministration guidelines. The valve commissure deflection for eachvalve was measured as shown in Table III. TABLE III Comm. 1 Comm. 2Comm. 3 Valve Actual Actual Actual Average Std. No. Cycle No. (mm) (mm)(mm) (mm) Dev. 13559 1 0.89 1.10 0.78 0.92 0.16 2 0.89 1.10 0.78 0.920.16 3 0.86 1.13 0.79 0.93 0.18 13560 1 1.05 1.39 1.21 1.22 0.17 2 1.021.39 1.23 1.21 0.19 3 1.05 1.42 1.23 1.23 0.19 13561 1 1.26 1.32 1.071.22 0.13 2 1.26 1.36 1.08 1.23 0.14 3 1.23 1.32 1.08 1.21 0.12 13562 11.07 1.32 0.84 1.08 0.24 2 1.07 1.32 0.82 1.07 0.25 3 1.05 1.36 0.841.08 0.26 Average 1.11 Std. 0.16 Dev.

[0079] Proper coaptation was observed in valves 13559, 13560, and 13561,where the mismatch between leaflets 1 and 2 and leaflet 3 was less thanapproximately 0.030″. Thus, from this particular study, leaflets whichhave deflection values differing by less than approximately 0.030″ aresuitably grouped for combining in a heart valve. Of course, this testapplies to 29 mm CEP valves made from selected bovine pericardium, andthere are a variety of parameters which could alter the conclusionregarding acceptable deflection correlation. Furthermore, the conclusionwas based on measured valve commissure deflection, which is onepredictor of prolonged leaflet coaptation. A desirable selectionmethodology, therefore, is to obtain a collection of similarly sizedleaflets, apply a load to each leaflet, observe the resulting strainresponse, and sort the leaflets based on their respective strainresponses. Additionally, the leaflets are preferably chemically fixedprior to testing and a droop test is used in conjunction with thedeflection test results.

[0080] The present invention additionally teaches a multi-leafletbioprosthetic heart valve with leaflets selected to have observeddeflection responses within a certain range. The average deflection inthe range depends on a number of variables, as explained above, and thebreadth of the range may depend on empirical test results of assembledvalves, such as the commissure deflection data included in Table III. Inone exemplary embodiment, however, a 29 mm multi-leaflet bioprostheticCEP heart valve comprising glutaraldehyde-fixed bovine pericardiumtissue leaflets includes at least two leaflets having a deflection ofwithin 0.030 inches as measured using the exemplary testing method andapparatus, with a mass sufficient to create stresses in the leaflets ofbetween 300 and 600 kPa

[0081] It should be noted that the present invention is best suited forcategorizing and selecting leaflets having varying material propertiesfrom leaflet to leaflet, such as in bovine pericardium. Recent advancesin bioprosthetic materials enable manufacturers to produce leaflets bygrowing tissue on a matrix. Such material may also exhibitnonuniformities in individual leaflets and could be grouped and/orselected in accordance with the present invention. Another type oftissue for which the present invention may prove valuable in selectingleaflets is a composite or laminate substrate on which a cell growthcovering is formed. Alternatively, the present selection methods andapparatuses may be applicable to leaflets made from materials with moreuniform properties, such as synthetically fabricated or extrudedcollagen sheets. Though the bulk material properties of these lattermaterials may be more predictable, individual testing of leaflets isbelieved desirable to more accurately assess the subsequent dynamicresponse of the leaflets in use. In addition, testing of leaflets usinga setup which closely simulates the particular heart valve in which theleaflet will be used is desirable, in addition to the pre-existingknowledge of the material properties. For these more uniform leaflets,testing of a sample of leaflets from a specific manufactured batch maysuffice.

[0082] In closing it is to be understood that the embodiments of theinvention disclosed herein are illustrative of the principles of theinvention and that other modifications may be employed which are withinthe scope thereof. Accordingly, the present invention is not limited tothat precisely as shown and described in the specification.

What is claimed:
 1. An implantable heart valve manufactured by a processcomprising the steps of: providing a collection of similarly sizedleaflets; applying a load to each leaflet; observing the strain responsein each leaflet caused by applying the load; sorting the leaflets intosubgroups based on their respective strain responses such that theleaflets in each subgroup each have a strain response within apredetermined range; and, attaching only leaflets from a single subgroupto the heart valve such that when fluid pressure is applied to theimplantable heart valve the leaflets thereon will exhibit similar strainresponse.
 2. The implantable heart valve of claim 1, wherein the step ofproviding a collection includes providing a collection of natural tissueleaflets.
 3. The implantable heart valve of claim 2, further includingthe step of chemically fixing the leaflets prior to testing.
 4. Theimplantable heart valve of claim 2, wherein the step of providing acollection of natural tissue leaflets includes providing a collection ofbovine pericardium leaflets.
 5. The implantable heart valve of claim 1,wherein the step of providing a collection of leaflets includesproviding a collection of leaflets having a matrix and natural tissueingrowth.
 6. The implantable heart valve of claim 1, wherein the step ofproviding a collection of leaflets includes providing a collection ofleaflets having a substrate on which is formed a cell growth covering.7. The implantable heart valve of claim 1, wherein the step of providinga collection of leaflets includes providing a collection of extrudedcollagen leaflets.
 8. The implantable heart valve of claim 1, whereinthe step of applying a load comprises applying a load sufficient tocreate an average stress in at least some of the leaflets within agenerally linear, high modulus region of a stress/strain curve of theleaflet material.
 9. The implantable heart valve of claim 1, furtherincluding the step of applying a load for a predetermined number oftimes prior to observing the strain response.
 10. The implantable heartvalve of claim 9, wherein the predetermined number is at least three.11. The implantable heart valve of claim 1, further including the stepsof: performing an intrinsic load test on the leaflets; and sorting theleaflets based on the intrinsic load test results.
 12. The implantableheart valve of claim 1, wherein the step of forming subgroups ofleaflets having a strain response within a predetermined range comprisesa measuring a deflection of each leaflet resulting from applying a loadthereto, and forming a subgroup of leaflets each having a deflectionwithin about 0.030 inches of the others.
 13. An implantable heart valvehaving multiple leaflets, wherein each leaflet has been tested by aprocess comprising the steps of: mounting the leaflet in a framingassembly so that portions which are to be sutured in the valve are heldstationary, wherein the leaflet defines a cusp edge and a coapted edgegenerally opposite the cusp edge, and the framing assembly includes anupper member and a lower member, the lower member having a recess forreceiving at least the cusp edge of the leaflet, the upper member beingshaped to mate over the recess, and the framing assembly defining acavity circumscribed by the recess, the step of mounting includingpositioning the leaflet in the recess and piercing the leaflet cusp edgewith needles extending between and supported from movement by the upperand lower members, to hold at least the cusp edge of the leafletstationary; applying a load to the leaflet in a location adapted tosimulate a point at which an average load is applied in the valve;sensing the resulting strain in the leaflet; sorting the leaflets intosubgroups based on their respective strain responses such that theleaflets in each subgroup have a strain response within a predeterminedrange; and, attaching only leaflets from a single subgroup to the heartvalve.
 14. The implantable heart valve of claim 13, wherein the step ofapplying a load comprises applying a mechanical deflector to an uppersurface of the leaflet over the cavity.
 15. The implantable heart valveof claim 13, further including the step of recording the sensed strain.16. The implantable heart valve of claim 15, further including applyinga load at least twice before recording the sensed strain.
 17. Theimplantable heart valve of claim 16, further including the step ofperforming a droop test on the leaflet by extending the leaflet over theend of a structure, and observing the resulting droop of the extendedend of the leaflet.
 18. The implantable heart valve of claim 17, furtherincluding testing a second leaflet and correlating the results of thedroop tests and applied load tests for the two leaflets.
 19. Theimplantable heart valve of claim 13, wherein the leaflet is made of aleaflet material, and the step of applying a load comprises applying aload sufficient to stress the leaflet within a generally linear highmodulus region of a stress/strain curve of the leaflet material.
 20. Theimplantable heart valve of claim 13, wherein the step of applying a loadcomprises applying a load sufficient to stress the leaflet between 300and 600 kPa.